Delayed Afterdepolarization in Intact Canine Sinoatrial Node as a Novel Mechanism for Atrial Arrhythmia

Methods and Results: We simultaneously mapped Ca-i and membrane potential in 31 isolated Langendorff-perfused canine right atriums (RA). Isoproterenol increased heart rate and late diastolic Ca-i elevation (LDCAE) of the superior SAN, leading to consistent SAN automaticity in all 31 RAs. However, DAD-like diastolic depolarizations (DD) were transiently observed in 4 RAs during isoproterenol infusion. These DAD-like DDs were preceded by LDCAE, but did not trigger a full action potential. The LDCAE preceding DAD-like DDs had smaller amplitude (0.41 +/- 0.08 AU vs 0.48 +/- 0.07 AU, P = 0.001) and less steep slopes (3.7 +/- 1.3 AU/s vs 4.8 +/- 1.4 AU/s, P = 0.001) than that of sinus beats. The coupling interval of DAD-like DDs was longer than that of the preceding normal beats (407 +/- 48 ms vs 371 +/- 44 ms, P = 0.002). Conclusion: The isoproterenol-induced LDCAE of superior SAN induced a full action potential in most cases. However, if the LDCAE was too small to trigger an action potential, then it induces only DAD-like DD. The failure of DAD-like DD to consistently trigger a sinus beat is a novel mechanism of atrial arrhythmogenesis. (J Cardiovasc Electrophysiol, Vol. 22, pp. 448-454).